Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

NCT ID: NCT01549964

Last Updated: 2016-06-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 916 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this study is to evaluate the efficacy of 2 doses of TAK-875 (25 mg and 50 mg), once daily (QD), plus metformin compared to placebo plus metformin and sitagliptin plus metformin on lowering blood sugar.

Detailed Description

TAK-875 is being developed at Takeda Development Center, Inc. as an adjunct to diet and exercise to improve glycemic control in participants with Type 2 Diabetes Mellitus (T2DM) whose blood glucose level is inadequately controlled with metformin.

This study will evaluate the efficacy of TAK-875 (25 mg and 50 mg) plus metformin compared to placebo plus metformin and sitagliptin plus metformin on glycemic control as measured by change from baseline in glycosylated hemoglobin (HbA1c) over a 24-week Treatment Period. Participants completing the 24-week Treatment Period may enter an optional 80-week extension period for a total of 104 weeks of treatment.

Due to concerns about potential liver safety, on balance, the benefits of treating patients with fasiglifam (TAK-875) do not outweigh the potential risks.

For this reason, Takeda has decided voluntarily to terminate the development activities for fasiglifam.

Conditions

Glycemic Control

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fasiglifam (TAK-875) 25 mg

Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Group Type: EXPERIMENTAL

Fasiglifam (TAK-875)

Intervention Type: DRUG

Fasiglifam (TAK-875) tablets

Fasiglifam (TAK-875) 50 mg

Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Group Type: EXPERIMENTAL

Fasiglifam (TAK-875)

Intervention Type: DRUG

Fasiglifam (TAK-875) tablets

Sitagliptin 100 mg

Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

Sitagliptin tablets

Placebo

Fasiglifam (TAK-875) placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo-matching tablets

Interventions

Fasiglifam (TAK-875)

Fasiglifam (TAK-875) tablets

Intervention Type: DRUG

Sitagliptin

Sitagliptin tablets

Intervention Type: DRUG

Placebo

Placebo-matching tablets

Intervention Type: DRUG

Other Intervention Names

Januvia

Eligibility Criteria

Inclusion Criteria

1. The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.

2. The participant meets one of the following criteria:

1. The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose [MTD]) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;

2. The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and <10.5%.

3. The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening).

4. The participant has a body mass index (BMI) ≤45 kg/m² at Screening.

5. Participants regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.

6. The participant is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete subject diaries.

Exclusion Criteria

1. The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.

2. Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit.

3. The participant has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Visit. (If the participant meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.)

4. The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.

5. The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.

6. The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senior Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Muscle Shoals, Alabama, United States

Mesa, Arizona, United States

Peoria, Arizona, United States

Phoenix, Arizona, United States

Chula Vista, California, United States

El Cajon, California, United States

La Mesa, California, United States

Laguna Hills, California, United States

National City, California, United States

Paramount, California, United States

San Diego, California, United States

Stockton, California, United States

Tustin, California, United States

West Hills, California, United States

Trumbull, Connecticut, United States

Coral Gables, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

New Port Richey, Florida, United States

Ocala, Florida, United States

West Palm Beach, Florida, United States

Meridian, Idaho, United States

Chicago, Illinois, United States

Greenfield, Indiana, United States

Muncie, Indiana, United States

Lexington, Kentucky, United States

Owensboro, Kentucky, United States

Hyattsville, Maryland, United States

Troy, Michigan, United States

Picayune, Mississippi, United States

St Louis, Missouri, United States

Haddon Heights, New Jersey, United States

Rosedale, New York, United States

Calabash, North Carolina, United States

Charlotte, North Carolina, United States

Monroe, North Carolina, United States

Morehead City, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Dayton, Ohio, United States

Norman, Oklahoma, United States

Lancaster, Pennsylvania, United States

Levittown, Pennsylvania, United States

Spartanburg, South Carolina, United States

Crossville, Tennessee, United States

Memphis, Tennessee, United States

Carrollton, Texas, United States

Houston, Texas, United States

Irving, Texas, United States

Katy, Texas, United States

McKinney, Texas, United States

Plano, Texas, United States

San Antonio, Texas, United States

Spring, Texas, United States

Salt Lake City, Utah, United States

West Jordan, Utah, United States

Richmond, Virginia, United States

Camperdown, New South Wales, Australia

Maroubra, New South Wales, Australia

Redcliffe, Queensland, Australia

Adelaide, South Australia, Australia

Daw Park, South Australia, Australia

Box Hill, Victoria, Australia

Fitzroy, Victoria, Australia

Melbourne, Victoria, Australia

Byala, , Bulgaria

Kazanlak, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Čakovec, , Croatia

Karlovac, , Croatia

Krapinske Toplice, , Croatia

Rijeka, , Croatia

Slavonski Brod, , Croatia

Split, , Croatia

Zadar, , Croatia

Zagreb, , Croatia

Beroun, , Czechia

Brno, , Czechia

Havlíčkův Brod, , Czechia

Kladno, , Czechia

Kroměříž, , Czechia

Mladá Boleslav, , Czechia

Ostrava, , Czechia

Ostrava - Moravska Ostrava, , Czechia

Pardubice, , Czechia

Pilsen, , Czechia

Písek, , Czechia

Prague, , Czechia

Ústí nad Labem, , Czechia

Baja, , Hungary

Balatonfüred, , Hungary

Budaörs, , Hungary

Budapest, , Hungary

Debrecen, , Hungary

Eger, , Hungary

Gödöllő, , Hungary

Gyöngyös, , Hungary

Gyula, , Hungary

Hódmezővásárhely, , Hungary

Kecskemét, , Hungary

Kistelek, , Hungary

Kisvárda, , Hungary

Komárom, , Hungary

Mohács, , Hungary

Nyíregyháza, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Szekszárd, , Hungary

Szikszó, , Hungary

Szolnok, , Hungary

Szombathely, , Hungary

Úrhida, , Hungary

Veszprém, , Hungary

Zalaegerszeg, , Hungary

Florence, Firenze, Italy

Milan, Milano, Italy

Sesto San Giovanni, Milano, Italy

Pavia, Pavia, Italy

Johor Bahru, Johor, Malaysia

Alor Star, Kedah, Malaysia

Kelantan, Kelantan, Malaysia

Kota Bharu, Kelantan, Malaysia

Cheras, Kuala Lumpur, Malaysia

Kuala Lumpur, Kuala Lumpur, Malaysia

Lembah Pantai, Kuala Lumpur, Malaysia

Petaling Jaya, Selangor, Malaysia

Banská Bystrica, , Slovakia

Bardejov, , Slovakia

Bratislava, , Slovakia

Kosice - Saca, , Slovakia

Košice, , Slovakia

Levice, , Slovakia

Lučenec, , Slovakia

Moldava nad Bodvou, , Slovakia

Nitra, , Slovakia

Pezinok, , Slovakia

Prešov, , Slovakia

Prievidza, , Slovakia

Stropkov, , Slovakia

Svidník, , Slovakia

Šahy, , Slovakia

Štúrovo, , Slovakia

Trebišov, , Slovakia

Trenčín, , Slovakia

Žilina, , Slovakia

Goyang-si, Gyeonggi-do, South Korea

Seongnam-si, Gyeonggi-do, South Korea

Incheon, , South Korea

Seoul, , South Korea

Bangkok, Bangkok, Thailand

Patumwan, Bangkok, Thailand

Rachathevi, Bangkok, Thailand

Rajtevi, Bangkok, Thailand

Ratchathewi, Bangkok, Thailand

Khon Kaen, Changwat Khon Kaen, Thailand

Muang, Changwat Nakhon Ratchasima, Thailand

Hat Yai, Changwat Songkhla, Thailand

Muang, Chiang Mai, Thailand

Countries

United States; Australia; Bulgaria; Croatia; Czechia; Hungary; Italy; Malaysia; Slovakia; South Korea; Thailand

References

Shavadia JS, Sharma A, Gu X, Neaton J, DeLeve L, Holmes D, Home P, Eckel RH, Watkins PB, Granger CB. Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program. Clin Trials. 2019 Jun;16(3):253-262. doi: 10.1177/1740774519836766. Epub 2019 Mar 18.

Reference Type: DERIVED

PMID: 30880443 (View on PubMed)

Other Identifiers

2011-001752-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1124-2225

Identifier Type: REGISTRY

Identifier Source: secondary_id

NMRR-12-446-11314

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-875_302

Identifier Type: -

Identifier Source: org_study_id